Striatal and urinary DOPAC/DA ratio may indicate a long-lasting DA release enhancement by MPP+ and MPTP.
The DOPAC/DA ratio in mouse striatum, in striatal synaptosomes, and in rat urine after MPP+ and MPTP neurotoxin administrations to the animals was followed temporally. The neurotoxins were given intraperitoneally and, in some experiments, to enhance the sensitivity, the animals were subsequently reserpinized before either sacrifice or 24 hour urine collection. MPP+ treatment, followed by saline, weakly lowered mouse striatal DOPAC/DA ratio up to 6 hours; in reserpinized animals, however, the neurotoxin reduced striatal ratio potently and for longer periods. Similarly, MPP+ reduced rat (saline treated) urinary DOPAC level and DOPAC/DA ratio in the short term (1.0 hr) while the neurotoxin effects could still be detected following longer periods up to 27 days in reserpinized animals. A single MPTP treatment (90 min.), followed by preparation of striatal synaptosomal fraction and its incubation (37 degrees C) with or without reserpine, also led to a reduced DOPAC/DA ratio. Although mainly the pooled peripheral effect is directly indicated by urinary DOPAC/DA ratio, MPP+ may reduce DA oxidation in the CNS and may similarly affect the amine oxidation in the peripheral tissues. The CNS and peripheral effects differ, however, in respect to dose-sensitivity and time course. The similarities between the CNS and peripheral effects suggest that a blunted rise of urinary DOPAC/DA ratio after reserpine challenge could be utilized as a peripheral marker of MPP+ action in the CNS, a marker that is not currently available.
Bagchi
S P
SP
Nathan S. Kline Institute for Psychiatric Research, Orangeburg, New York 10962.
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism / Q000652:urine*; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism / Q000652:urine*; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D011726:Pyridinium Compounds / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D012110:Reserpine / Q000494:pharmacology; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
D011726:Pyridinium Compounds; D015102:3,4-Dihydroxyphenylacetic Acid; C026560:1-(4-methoxyphenyl)pyridinium; D012110:Reserpine; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D004298:Dopamine